BMC Nephrology
·
2019
·Vol. 20
·期 1
·1-7
·
IF 2.088
Xiong Ruifang,Lu Xiangxue,Song Jinghong,Li Han,Wang Shixiang
Background Cardiovascular disease is the most common complication and leading cause of death in maintenance hemodialysis patients. The protection mechanism of hydrogen sulfide (H2S) and the specific role of conventional protein kinase C βII (cPKCβII)/Akt signaling pathway in the formation of atherosclerosis is still controversial.Methods 8-week-old male ApoE−/− mice were treated with 5/6 nephrectomy and high-fat diet to make uremia accelerated atherosclerosis (UAAS) model. Mice were divided into normal control group (control group), sham operation group (sham group), UAAS group, L-cysteine group (UAAS+L-cys group), sodium hydrosulfide group (UAAS+NaHS group), and propargylglycine group (UAAS+PPG group). Western blot was used to detect cPKCβII activation, Akt phosphorylation and endothelial nitric oxide synthase (eNOS) expression in mice aorta.Results The membrane translocation of cPKCβII in UAAS group was higher than sham group, and L-cys or NaHS injection could suppress the membrane translocation, but PPG treatment resulted in more membrane translocation of cPKCβII (P < 0.05, n = 6 per group). Akt phosphorylation and the eNOS expression in UAAS group was lower than sham group, and L-cys or NaHS injection could suppress the degradation of Akt phosphorylation and the eNOS expression, but PPG treatment resulted in more decrease in the Akt phosphorylation and the eNOS expression (P < 0.05, n = 6 per group).Conclusion Endogenous cystathionine-γ-lyase (CSE)/H2S system protected against the formation of UAAS via cPKCβII/Akt signal pathway. The imbalance of CSE/H2S system may participate in the formation of UAAS by affecting the expression of downstream molecule eNOS, which may be mediated by cPKCβII/Akt signaling pathway.
研究领域:
心血管疾病
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分子生物学
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动物模型
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信号转导
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DOI
PubMed
高影响因子
Pharmaceutics
·
2022
·Vol. 14
·期 11
·2534
·
IF 6.525
Bo Wei,Yuanfang Li,Meiying Ao,Wenxiang Shao,Kun Wang,Tong Rong,Yun Zhou,Yong Chen
Previously, we found that exogenous ganglioside GM3 had an antiatherosclerotic efficacy and that its antiatherosclerotic efficacy could be enhanced by reconstituted high-density lipoprotein (rHDL). In this study, we hypothesized that GM3-functionalized rHDL (i.e., GM3-rHDL) as a nanocarrier can promote the efficacy of traditional antiatherosclerotic drugs (e.g., statins). To test this hypothesis, lovastatin (LT) was used as a representative of statins, and LT-loaded GM3-rHDL nanoparticle (LT-GM3-rHDL or[email protected]; a mean size of ~142 nm) and multiple controls (e.g., GM3-rHDL without LT, LT-loaded rHDL or LT-rHDL, and other nanoparticles) were prepared. By using two different microsphere-based methods, the presences of apolipoprotein A-I (apoA-I) and/or GM3 in nanoparticles and the apoA-I-mediated macrophage-targeting ability of apoA-I/rHDL-containing nanoparticles were verified in vitro. Moreover, LT-GM3-rHDL nanoparticle had a slowly sustained LT release in vitro and the strongest inhibitory effect on the foam cell formation of macrophages (a key event of atherogenesis). After single administration of rHDL-based nanoparticles, a higher LT concentration was detected shortly in the atherosclerotic plaques of apoE−/−mice than non-rHDL-based nanoparticles, suggesting the in vivo plaque-targeting ability of apoA-I/rHDL-containing nanoparticles. Finally, among all nanoparticles LT-GM3-rHDL induced the largest decreases in the contents of blood lipids and in the areas of atherosclerotic plaques at various aortic locations in apoE−/−mice fed a high-fat diet for 12 weeks, supporting that LT-GM3-rHDL has the best in vivo antiatherosclerotic efficacy among the tested nanoparticles. Our data imply that GM3-functionalized rHDL (i.e., GM3-rHDL) can be utilized as a novel nanocarrier to enhance the efficacy of traditional antiatherosclerotic drugs (e.g., statins).Keywords:ganglioside GM3;atherosclerosis;reconstituted high-density lipoprotein (rHDL);lovastatin (LT);drug delivery system;statins;ApoA-I
研究领域:
药理学
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心血管疾病
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纳米技术
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药物递送
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DOI
PubMed
高影响因子
Nutrients
·
2023
·Vol. 15
·期 4
·973
·
IF 5.9
Haiyan Zhou,Wenjing Liu,Yiqian Lv,Ke Liu,Yin Wang,Shuangli Meng,Tong Kang,Yuechao Bao,Huicui Meng
We aimed to examine the effect of natto and red yeast rice (NR) supplementation on lipid and lipoprotein profiles, gene expressions of cholesterol metabolism, and the composition of gut microbiota in ApoE-/-mice. Forty-one male ApoE-/-mice aged 7–8 wks old were randomly fed a control diet (CD), CD + NR (oral gavage at 0.3 g/kg BW/day), high-fat and high-cholesterol diet (HFD), or HFD + NR for 12 wks. Fasting blood samples, liver and intestine tissues and fecal samples were collected at week 12. Biochemical parameters, gene expressions in cholesterol metabolism and gut microbiota composition and diversity were measured using standard methods. NR supplementation had no significant effect on lipid and lipoprotein profiles. Compared with the HFD group, HFD + NR resulted in higher mRNA expressions of HMGCR and CYP7A1 (bothP-NR< 0.05) and ABCA1 (P-diet*NR= 0.0134,P-NR= 0.0407), lower mRNA expression of PCSK9 (P-diet*NR= 0.0002), lower fasting glucose concentrations (P-diet*NR= 0.0011), and lower relative abundance of generaBacteroidesandLactococcus(bothP-NR< 0.01) andCoriobacteriaceae_UCG-002(P-diet*NR= 0.0007). The relative abundance ofLactococcuswas inversely correlated with HMGCR and CYP7A1, and the relative abundance ofCoriobacteriaceae_UCG-002was positively correlated with PCSK9 and inversely correlated with ABCA1 (allP< 0.05). These findings suggest that NR supplementation may regulate gene expressions in cholesterol metabolism via changes in the gut microbiota in HFD-fed ApoE-/-mice.Keywords:natto;red yeast rice;gene expression;cholesterol metabolism;gut microbiota
研究领域:
营养学
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分子生物学
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胃肠病学
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DOI
PubMed
高影响因子
MICROCHEMICAL JOURNAL
·
2024
·
IF 4.9
Gangyuan Lin,Qidi He,Jiadong Cai,Xiujuan Yang,Yong Wang
Single-nucleotide polymorphisms (SNPs) can be relevant to disease susceptibility, disease pathogenesis, and efficacy of specific drugs. Monitoring SNPs plays a significant role in disease susceptibility and individual response to treatment, wherein optimal care can be provided to individuals based on their unique genetic and disease profiles. In this work, we have formulated a rapid and sensitive fluorescent biosensing platform based on a target-activated triple-helix molecular switch (THMS)-conformation-change-induced invader assay strategy for the detection of single nucleotide polymorphisms in the apolipoprotein E ( APOE ). The mutant DNA (MtDNA) of APOE gene hybridized with the THMS to form the three-dimensional invader structure over the SNP site. Subsequently, the specific structure would be recognized and cleaved by FEN1, leading to the recovery of FAM quenched by BHQ 1. Based on the high binding affinity of THMS to the target, our strategy could detect the MtDNA of AOPE gene without amplification at 0.27 nM. Furthermore, we achieved genotyping based on the difference in fluorescence signals and successfully applied this strategy to detect MtDNA of APOE gene in clinical samples, showing the great potential for monitoring various SNPs for biological research and disease diagnosis.
研究领域:
分子生物学
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医学诊断
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遗传学
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DOI
高影响因子
Nanoscale
·
2015
·Vol. 7
·期 17
·7682-7691
·
IF 7.394
Zhiyou Peng,Jinbao Qin,Bo Li,Kaichuang Ye,Yuxin Zhang,Xinrui Yang,Fukang Yuan,Lijia Huang,Junqing Hu,Xinwu Lu
Photothermal therapy (PTT), as a promising treatment for tumours, has rarely been reported for application in artery restenosis, which is a common complication of endovascular management due to enduring chronic inflammation and abnormal cell proliferation. In our study, biodegradable polypyrrole nanoparticles (PPy-NPs) were synthesized and characterized, including their size distribution, UV-vis-NIR absorbance, molar extinction coefficients, and photothermal properties. We then verified that PPy-NP incubation followed by 915 nm near-infrared (NIR) laser irradiation could effectively ablate inflammatory macrophages in vitro, leading to significant cell apoptosis and cell death. Further, it was found that a combination of local PPy-NP injection with 915 nm NIR laser irradiation could significantly alleviate arterial inflammation by eliminating infiltrating macrophages and further ameliorating artery stenosis in an ApoE−/− mouse model, without showing any obvious toxic side effects. Thus, we propose that PTT based on PPy-NPs as photothermal agents and a 915 nm NIR laser as a power source can serve as a new effective treatment for reducing inflammation and stenosis formation in inflamed arteries after endovascular management.
研究领域:
生物医学工程
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心血管疾病
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纳米技术
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治疗方法
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DOI
PubMed
高影响因子
Journal of Pharmaceutical Analysis
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2024
·
IF 6.1
Zhenjie Yu,Huarong Shao,Xintian Shao,Linyan Yu,Yanan Gao,Youxiao Ren,Fei Liu,Caicai Meng,Peixue Ling,Qixin Chen
Unlike chemosynthetic drugs designed for specific molecular and disease targets, active small-molecule natural products typically have a wide range of bioactivities and multiple targets, necessitating extensive screening and development. To address this issue, we propose a strategy for the direct in situ microdynamic examination of potential drug candidates to rapidly identify their effects and mechanisms of action. As a proof-of-concept, we investigated the behavior of mussel oligosaccharide (MOS-1) by tracking the subcellular dynamics of fluorescently labeled MOS-1 in cultured cells. We recorded the entire dynamic process of the localization of fluorescein isothiocyanate (FITC)-mussel oligosaccharide (MOS-1) to the lysosomes and visualized the distribution of the drug within the cell. Remarkably, lysosomes containing FITC-MOS-1 actively recruited lipid droplets, leading to fusion events and increased cellular lipid consumption. These drug behaviors confirmed MOS-1 is a candidate for the treatment of lipid-related diseases. Furthermore, in a high-fat HepG2 cell model and in high-fat diet-fed ApoE −/− mice, MOS-1 significantly promoted triglyceride degradation, reduced lipid droplet accumulation, lowered serum triglyceride levels, and mitigated liver damage and steatosis. Overall, our work supports the prioritization of in situ visual monitoring of drug location and distribution in subcellular compartments during the drug development phase as this methodology contributes to the rapid identification of drug indications. Collectively, this methodology is significant for the screening and development of selective small-molecule drugs, and is expected to expedite the identification of candidate molecules with medicinal effects.
研究领域:
药理学
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细胞生物学
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药物开发
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DOI
PubMed
高影响因子
Foods
·
2025
·Vol. 14
·期 24
·4267
·
IF 5.1
Jing Xu,Wen-Zhao Wen,Jun-Hui Zhao,Jun-Rong Guo,Zhuo-Ya Zhang,Ping Xiong
Citri grandis exocarpium ( Citri grandis ) has been consumed by human beings for fifteen hundred years. It is commonly consumed as a health drink and dietary supplement in China. However, its nutritional and healthcare functions are still not fully understood. Objective: Our previous study found that oral administration of Citri grandis extract can significantly decrease the blood lipid levels of hyperlipidemic mice fed a high-fat diet. The aim of this study was to confirm the preventative effects of Citri grandis extract against atherosclerosis. Methods: Atherosclerotic lesion models were induced in HUVECs and apoE −/− C57BL/6J mice. ApoE −/− mice fed a high-fat diet were orally administered Citri grandis extract (0.4, 0.8, and 1.6 g/kg/d BW) and Simvastatin (1 mg/kg/d BW) on the first day of model establishment. After a 16-week treatment, serum samples and aorta and liver tissues were collected. Observation of pathological changes in aortic and liver tissues was performed using a light microscope with oil red O, H&E, Masson’s trichrome staining, and TEM. Biochemical detection was employed to determine the serum levels of TC, TG, LDL-C, and HDL-C as well as the activities of AST and ALT. In addition, expression studies of TGF-β, PI3K, AKT1, PPAR-γ, LXR-α, and ABCA1 were performed via qPCR and Western blot analysis. Results: Compared with cholesterol-induced HUVECs, Citri grandis extract significantly enhanced cell viability, attenuated the morphological changes in HUVECs, and reduced LDH release. Furthermore, after treatment with Citri grandis extract, the levels of TC, TG, and LDL-C significantly decreased in the atherosclerosis model apoE −/− mice after 16 weeks, and aortic plaque, lipid deposition, and endothelial injury were obviously ameliorated. The mRNA and protein expression of TGF-β, PPAR-γ, LXR-α, and ABCA1 in aortic and liver of atherosclerosis apoE −/− mice were upregulated ( p < 0.05, p < 0.01), while those of PI3K and Akt1 were suppressed ( p < 0.05, p < 0.01). Conclusions: Citri grandis extract can significantly decrease the high circulating lipid levels and the liver lipid deposition of high-fat-diet-fed apoE −/− mice and reduce aorta lipid accumulation and atherosclerotic plaques by regulating the expression of TGF-β1, PI3K, AKT1, PPAR-γ, LXR-α, and ABCA1. Citri grandis extract can be used as a healthcare dietary supplement for the prevention of abnormal lipid metabolism and atherosclerosis.
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PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2024
·
IF 4.8
Jie Du,Xinxin Zhu,Youqi Zhang,Xingtao Huang,Xuedong Wang,Fan Yang,Hongyuan Xia,Jingbo Hou
C1q/TNF-related protein 13 (CTRP13) is a secreted adipokine that has been shown to play an important role in a variety of cardiovascular diseases. However, the effect of CTRP13 on ferroptosis of endothelial cells and its underlying mechanism remain unclear. In the present study, we analyzed the effects of CTRP13 on endothelial dysfunction in high-lipid-induced ApoE −/− mice and ox-LDL-induced mouse aortic endothelial cells (MAECs). In vivo experiment: Male ApoE −/− mice fed high fat were given C1ql3 gene overexpression adeno-associated virus. The atherosclerotic plaque size, lipid content, collagen fiber proportion and iron deposition level were measured. In vitro, CTRP13 combined with ox-LDL was used to pretreat MAECs to detect cell survival rate, lipid peroxidation, iron ion deposition and mitochondrial level. In this study, CTRP13 was found to inhibit ferroptosis of endothelial cells, demonstrated by up-regulated the expression of ferroptosis protective protein glutathione Peroxidase 4 (GPX4), and decreased the expression of acyl-CoA synthetase long-chain family member 4 (ACSL4) protein. Mechanistically, gtp cyclohydrolase 1(GCH1) silencing or tetrahydrobiopterin (BH4) inhibiting may counteract the protective effect of CTRP13 on ox-LDL-induced ferroptosis of endothelial cells, which is characterized by decreased cell activity, mitochondrial damage, increased iron ion deposition and lipid peroxidation, decreased GPX4 expression, and increased ACSL4 expression. This study demonstrated for the first time that CTRP13 can improve mitochondrial oxidative stress, inhibit ferroptosis of endothelial cells and improve endothelial cell dysfunction by activating the GCH1/BH4 signaling pathway, thereby inhibiting the progression of atherosclerosis.
研究领域:
心血管疾病
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细胞生物学
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分子生物学
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病理生理学
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DOI
PubMed
高影响因子
EXPERIMENTAL CELL RESEARCH
·
2021
·
IF 3.905
Lili Tan,Jie Lu,Limin Liu,Lu Li
Atherosclerosis is the underlying contributing factor of cardiovascular disease, which is a process of inflammation and lipid-rich lesion. Macrophage-derived foam cell is a key hallmark of atherosclerosis and connected with various factors of lipid metabolism. Here, we showed that fatty acid binding protein 3 (FABP3) was upregulated in the aorta of ApoE −/- mice with high-fat-diet (HFD) feeding. Knockdown of FABP3 in HFD-fed ApoE −/- mice notably facilitated cholesterol efflux, inhibited macrophage foam cell formation, and thus prevented atherogenesis. Furthermore, FABP3 silencing decreased the expression of peroxisome proliferator-activated receptor γ (PPARγ). Mechanistic studies had disclosed the involvement of PPARγ signaling in balancing cholesterol uptake and efflux and diminishing foam cell formation. These findings firstly revealed an anti-atherogenic role of FABP3 silencing in preventing foamy macrophage formation partly through PPARγ, which might be a beneficial approach for therapying atherosclerosis.
研究领域:
心血管疾病
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脂质代谢
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炎症
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产品关联
DOI
PubMed
高影响因子
Adipocyte
·
2022
·
IF 3.553
Shuai Chen,Yicheng Jiang,Xiaoyang Qi,Peng Song,Liming Tang,Hanyang Liu
Bariatric surgery (BS) is a dependable method for managing obesity and metabolic diseases, however, the regulatory processes of lipid metabolism are still not well elucidated. Differentially expressed genes (DEGs) were analysed through three transcriptomic datasets of GSE29409, GSE59034 and GSE72158 from the GEO database regarding subcutaneous adipose tissue (SAT) after BS, and 37 DEGs were identified. The weighted gene co-expression network analysis (WGCNA), last absolute shrinkage and selection operator (LASSO) logistic regression and support vector machine-recursive feature elimination (SVM-RFE) algorithms further screened four key genes involved in the regulation of STMN2, SFRP4, APOE and MXRA5. The GSE53376 dataset was used to further confirm the differential expression of SFRP4, APOE and MXRA5 in the postoperative period. GSEA analysis reveals activation of immune-related regulatory pathways after surgery. Finally, the silencing of MXRA5 was found by experimental methods to affect the expression of PPARγ and CEBPα during the differentiation of preadipocytes, as well as to affect the formation of lipid droplets. In conclusion, SAT immunoregulation was mobilized after BS, while MXRA5 was involved in the regulation of lipid metabolism.
研究领域:
生物信息学
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分子生物学
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代谢
·
肥胖
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DOI
PubMed
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
·
2020
·
IF 3.69
Yaxin Zhang,Yuyan Gu,Yihao Chen,Zhiyong Huang,Mei Li,Weihao Jiang,Jiahui Chen,Wenting Rao,Shangfei Luo,Yuyao Chen,Junqi Chen,Lijun Li,Yuhua Jia,Menghua Liu,Fenghua Zhou
Ethnopharmacological relevance Dingxin Recipe (DXR) is a traditional Chinese medicine formula that has been reported to be effective and safe treatment for cardiovascular diseases, such as arrhythmias, coronary heart disease. Dingxin Recipe IV (DXR IV) was further improved from the DXR according to the traditional use. However, the mechanism of DXR IV in atherosclerosis is unclear. Aim of the study This study aimed to illustrate whether DXR IV improve atherosclerosis through modulating the lipid metabolism and gut microbiota in atherosclerosis mice. Materials and methods 40 male ApoE -/- mice were fed on HFD for 12 weeks and were then treated with DXR IV (1.8, 0.9, or 0.45 g/kg/d) for another 12 weeks. The decroation of DXR IV contains four traditional Chinese medicines: the dried rhizome of Coptis chinensis Franch. (15.09%), the root of Salvia miltiorrhiza Bunge (28.30%), the seed of Ziziphus jujuba Mill. (37.74%) and the fruiting body of Ganoderma lucidum (Leyss.ex Fr.) Karst. (18.87%). 8 male c57BL/6 mice fed a normal diet served as control group. The atherosclerotic plaque was quantified by oil-red O staining and masson trichrome staining. Mice feces were collected. The gut micobiota were detected by 16S rRNA gene sequencing and fecal metabolites were analyzed by 1 H NMR spectroscopy. The effect of DXR IV on blood lipids (TG, TC, LDL-C, HDL-C) was investigated. The lipid metabolism related genes were determined by RT-qPCR and western blotting respectively. Results DXR IV exerted the anti-atherosclerosis effect by inhibiting the excessive cholesterol deposition in aorta and regulating the level of TG, TC, LDL-C and HDL-C. The composition of gut microbiota was changed. Interestingly, the relative abundance of Muribaculaceae and Ruminococcaceae increased after DXR IV administration, whereas the abundance of Erysipelotrichaceae decreased, which have been beneficial to lipid metabolism. Nine potential metabolic biomarkers, including acetate, butyrate, propionate, alanine, succinate, valerate, xylose, choline, glutamate, were identified, which were related to fatty acid metabolism. Further, the pathway of fatty acid was detected by the RT-qPCR and western blotting. Compared with model group, the level of LXR-α and SREBP1 decreased significantly in DXR IV group while LXR-β, SREBP2 showed no statistical significance. It indicated that DXR IV modulated lipid metabolism by LXR-α/SREBP1 but not LXRβ and SREBP2. Conclusions DXR IV exhibits potential anti-atherosclerosis effect, which is closely related to lipid metabolism and the gut microbiota. This study may provide novel insights into the mechanism of DXR IV on atherosclerosis and a basis for promising clinical usage.
研究领域:
药理学
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心血管疾病
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民族药理学
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分子生物学
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微生物学
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DOI
PubMed
高影响因子
INTERNATIONAL IMMUNOPHARMACOLOGY
·
2023
·
IF 5.6
Weixin Li,Zhuqi Huang,Yue Luo,Yaqian Cui,Mingjiang Xu,Wu Luo,Gaojun Wu,Guang Liang
Atherosclerosis (AS) is a chronic inflammatory disease. Recent studies have showed that stimulator of interferon genes (STING), an important protein in innate immunity, mediates pro-inflammatory activation of macrophages in the development of AS. Tetrandrine (TET) is a natural bisbenzylisoquinoline alkaloid isolated from Stepania tetrandra and possesses anti-inflammatory activities, with unknown effects and mechanisms in AS. In this study, we explored the anti-atherosclerotic effects of TET and investigated the underlying mechanisms. Mouse primary peritoneal macrophages (MPMs) are challenged with cyclic guanosine monophosphate-adenosine monophosphate (cGAMP) or oxidized LDL (oxLDL). We found that pretreatment with TET dose-dependently inhibited cGAMP- or oxLDL-induced STING/ TANK-binding kinase 1 (TBK1) signaling, then suppressing nuclear factor kappa-B (NF-κB) activation and pro-inflammatory factor expression in MPMs. ApoE -/- mice were fed a high-fat diet (HFD) to develop an atherosclerotic phenotype. Administration of TET at 20 mg/kg/day significantly reduced HFD-induced atherosclerotic plaques, accompanied with decreased macrophage infiltration, inflammatory cytokine production, fibrosis, and STING/TBK1 activation in aortic plaque lesions. In summary, we demonstrate that TET inhibits STING/TBK1/NF-κB signaling pathway to reduce inflammation in oxLDL-challenged macrophages and alleviate atherosclerosis in HFD-fed ApoE -/- mice. These findings proved that TET could be a potential therapeutic candidate for the treatment of atherosclerosis-related diseases.
研究领域:
心血管疾病
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免疫学
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药理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）